Publications by authors named "Marsha Mailick"

78 Publications

Health profiles of adults with autism spectrum disorder: Differences between women and men.

Autism Res 2021 Jul 2. Epub 2021 Jul 2.

Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin, USA.

The purpose of the present study was to investigate the hypothesis that women with autism have poorer health compared with men with autism, and compared with women without autism. Utilizing electronic health records drawn from a single health care system serving over 2 million individuals, 2119 adults with diagnosed autism spectrum disorders were compared with age- and sex-matched controls. When considering health care utilization, we found evidence of multiplicative risk for conditions within some domains (i.e., nutrition conditions, neurologic disease, psychiatric conditions, and sleep disorders) such that women with autism spectrum disorder (ASD) experienced double jeopardy-meaning they had greater rates of health care utilization within a domain than what would separately be expected by virtue of being a woman and having ASD. For other domains (i.e., endocrine disorders, gastrointestinal disorders), the risk was additive such that being a female and having ASD were both associated with higher health care utilization, but there were no significant interaction effects. It was only with respect to one domain (cardiovascular) that rates of health care utilization were reflective of neither ASD diagnosis nor sex. Overall, our findings suggest that women with ASD are a vulnerable subgroup with high levels of health care utilization. LAY SUMMARY: This study asked whether women with autism have poorer health compared with men with autism, and compared with women without autism. To answer this question, we used data from electronic health records. We found that women with autism spectrum disorder (ASD) were at the greatest risk for health problems such as nutrition conditions, neurologic disease, psychiatric conditions, and sleep disorders. More research on health of women with ASD is needed.
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http://dx.doi.org/10.1002/aur.2563DOI Listing
July 2021

Verbal Ability, Behavior Problems, and Mother-Child Relationship Quality in Autism Spectrum Disorder.

J Autism Dev Disord 2021 Jun 15. Epub 2021 Jun 15.

Waisman Center, University of Wisconsin-Madison, Madison, USA.

This study examined differences in mother-child relationship quality and parent-rated child behavior problems based on child verbal status (i.e., minimally verbal versus verbal) in mothers and their adolescent and adult children with autism spectrum disorder (n = 219 dyads; child M = 25.38 years, SD = 10.22). Relationship quality was assessed via parent-reported maternal burden and mother-child closeness, and coded speech samples ascertaining maternal critical and positive remarks regarding the child. Groups did not differ in relationship quality. The verbal group was more likely to display disruptive and socially inappropriate behaviors, but otherwise the groups did not differ in behavior problems. Verbal status moderated the relationship between behavior problems and negative (maternal burden, critical remarks) but not positive (mother-child closeness, positive remarks) aspects of relationship quality.
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http://dx.doi.org/10.1007/s10803-021-05133-2DOI Listing
June 2021

Mild Neurological Signs in FMR1 Premutation Women in an Unselected Community-Based Cohort.

Mov Disord 2021 Jun 12. Epub 2021 Jun 12.

Department of Neurological Sciences, Rush University, Chicago, Illinois, USA.

Background: Premutation-sized (55-200) CGG repeat expansions in the FMR1 gene cause fragile X-associated tremor/ataxia syndrome (FXTAS). Most studies of premutation carriers utilized reverse ascertainment to identify patients, leading to a selection bias for larger repeats. As shorter CGG premutation repeats are common in the population, understanding their impact on health outcomes has a potentially large public health footprint.

Objective: The study's objective was to compare an unselected group of premutation carriers (n = 35, 55-101 CGG repeats) with matched controls (n = 61, 29-39 CGG repeats) with respect to FXTAS-type signs using structured neurological assessments.

Methods: Three neurologists independently rated signs, using an adapted version of the FXTAS Rating Scale (Leehey MA, Berry-Kravis E, Goetz CG, et al. FMR1 CGG repeat length predicts motor dysfunction in premutation carriers. Neurology. 2008). This was a double-blind study, as genetic status (premutation vs. control) was known neither by the participants nor by any of the neurologists. Analyses controlled potentially confounding comorbid conditions in the electronic health record (eg, osteoarthritis and stroke) and probed the association of age with signs.

Results: Although there was no overall difference between carriers and controls, among individuals without any potentially confounding comorbid diagnoses, there was a statistically significant age-associated elevation in FXTAS-type signs in premutation carriers compared to controls.

Conclusions: Among those who do not have other comorbid diagnoses, women who have CGG repeats at the lower end of the premutation range may be at greater risk for ataxia and parkinsonism than their age peers, although their overall risk of developing such clinical features is low. This study should provide reassurance to those who share characteristics with the present cohort. © 2021 International Parkinson and Movement Disorder Society.
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http://dx.doi.org/10.1002/mds.28683DOI Listing
June 2021

Stress and genetics influence hair cortisol in FMR1 premutation carrier mothers of children with fragile X syndrome.

Psychoneuroendocrinology 2021 Jul 13;129:105266. Epub 2021 May 13.

Waisman Center, University of Wisconsin-Madison, United States.

To investigate genetic and environmental influences on cortisol levels, mothers of children with fragile X syndrome (FXS) were studied four times over a 7.5-year period. All participants (n = 84) were carriers of the FMR1 "premutation", a genetic condition associated with impaired HPA axis functioning. Genetic variation was indicated by expansions in the number of CGG (cytosine-guanine-guanine) repeats in the FMR1 gene (67-138 repeats in the present sample). The environmental factor was cumulative exposure to adverse life events during the study period. Cortisol was measured at the beginning of the study via saliva samples and at the end of the study via hair samples; hormone values from these two specimen types were significantly correlated. The interactions between CGG repeat number and adverse life events significantly predicted hair cortisol concentration, including after accounting for the initial salivary cortisol level. For those with fewer CGG repeats, stress exposure was associated with elevated cortisol, the expected response to stress, although women with a higher number of CGGs had a reduced cortisol response to adverse events, which might be related to HPA dysfunction. These results indicate that both exogenous and endogenous factors affect HPA functioning in this population of women.
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http://dx.doi.org/10.1016/j.psyneuen.2021.105266DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8217368PMC
July 2021

Who Returns? Understanding Varieties of Longitudinal Participation in MIDUS.

J Aging Health 2021 May 17:8982643211018552. Epub 2021 May 17.

5228University of Wisconsin-Madison, Madison, WI, USA.

This study describes a major effort to reinstate dropouts from the MIDUS longitudinal study and compare baseline characteristics among subgroups of participants to better understand predictors of retention, attrition, and reinstatement. All living dropouts were contacted, and 651 reinstated participants were interviewed in person (31.4% response rate). Age, gender, education, marital status, parental status, and physical and mental health were compared among the following groups: longitudinal sample, reinstated sample, those fielded for reinstatement who did not return, and those who dropped out at the 2nd or 3rd wave. Multivariate analyses revealed that reinstated participants were younger, male, unmarried, and less educated and had children at baseline compared to longitudinal participants. Reinstatement was unsuccessful among those with poorer mental health at baseline compared to longitudinal participants. This study informs reinstatement efforts, adjustment for attrition bias, and use of to examine aging consequents of early life vulnerability.
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http://dx.doi.org/10.1177/08982643211018552DOI Listing
May 2021

Artificial intelligence-assisted phenotype discovery of fragile X syndrome in a population-based sample.

Genet Med 2021 Jul 26;23(7):1273-1280. Epub 2021 Mar 26.

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.

Purpose: Fragile X syndrome (FXS), the most prevalent inherited cause of intellectual disability, remains underdiagnosed in the general population. Clinical studies have shown that individuals with FXS have a complex health profile leading to unique clinical needs. However, the full impact of this X-linked disorder on the health of affected individuals is unclear and the prevalence of co-occurring conditions is unknown.

Methods: We mined the longitudinal electronic health records from more than one million individuals to investigate the health characteristics of patients who have been clinically diagnosed with FXS. Additionally, using machine-learning approaches, we created predictive models to identify individuals with FXS in the general population.

Results: Our discovery-oriented approach identified the associations of FXS with a wide range of medical conditions including circulatory, endocrine, digestive, and genitourinary, in addition to mental and neurological disorders. We successfully created predictive models to identify cases five years prior to clinical diagnosis of FXS without relying on any genetic or familial data.

Conclusion: Although FXS is often thought of primarily as a neurological disorder, it is in fact a multisystem syndrome involving many co-occurring conditions, some primary and some secondary, and they are associated with a considerable burden on patients and their families.
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http://dx.doi.org/10.1038/s41436-021-01144-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257481PMC
July 2021

Brief Report: Socioeconomic Factors Associated with Minimally Verbal Status in Individuals with ASD.

J Autism Dev Disord 2021 Jun;51(6):2139-2145

Waisman Center, University of Wisconsin-Madison, 1500 Highland Ave., Madison, WI, 53705, USA.

About 30% of adults with autism are minimally verbal. Past research suggested that after age five, few gain verbal fluency, but studies have rarely investigated whether family environmental factors contribute to the acquisition of verbal fluency. The present study utilized data from the Autism Diagnostic Interview-Revised to compare changes in verbal fluency for 404 individuals with autism from childhood to adolescence and adulthood. Socioeconomic factors were examined across fluency groups (i.e., those who did/did not achieve verbal fluency). Findings indicated that fully 60% of those who were minimally verbal in early childhood acquired verbal fluency in adolescence and adulthood. Parent socioeconomic status differed across fluency groups, suggesting the importance of environmental factors for individual development.
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http://dx.doi.org/10.1007/s10803-020-04646-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943642PMC
June 2021

Longitudinal changes in well-being of parents of individuals with developmental or mental health problems.

Soc Sci Med 2020 11 21;264:113309. Epub 2020 Aug 21.

Department of Human Development and Family Studies, Pennsylvania State University, 335 Health and Human Development Building, University Park, PA, 16802, USA.

Rationale: A large body of work demonstrates the impact of caregiving burden on the well-being of parents of individuals with developmental conditions or mental health problems. However, a relative dearth of research examines this impact longitudinally into parents' older age.

Objective: The current study examines (1) longitudinal changes in the effect of having a child with a developmental or mental health problem on parental negative affect, psychological well-being, and somatic symptoms, (2) age and gender moderations on these effects, and (3) the unique impact of factors related to the child's condition.

Method: This study employs hierarchical linear regression models to examine longitudinal survey data from midlife adults (N = 1,101) from two waves of the National Study of Midlife in the United States (MIDUS).

Results: Models revealed some evidence for age attenuation of the impact of caregiving stress. Parents of children with developmental problems still had higher negative affect, poorer psychological well-being, and more somatic symptoms on average than parents in a comparison sample, whereas parents of children with mental health problems only showed evidence of higher negative affect compared to this sample. Within-group analyses also revealed differences between each parenting group into later adulthood.

Conclusions: Parents of individuals with developmental or mental health problems may be at risk for poorer well-being late in life. Yet, age and gender differences as well as diagnostic group differences nuance these findings.
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http://dx.doi.org/10.1016/j.socscimed.2020.113309DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7441882PMC
November 2020

The impact of parenting a child with serious mental illness: Accounting for the parent's genetic vulnerability to mental illness.

J Fam Psychol 2021 Apr 16;35(3):417-422. Epub 2020 Jul 16.

Waisman Center.

Parents of adults with serious mental illness (SMI) often are primary caregivers for their affected relative. Prior work has suggested that the toll of caregiving is associated with poorer well-being in family caregivers, particularly parents of affected adults. However, due to methodological limitations, it has not been possible to assess these family caregivers' own genetic vulnerability to mental and physical health problems, and thus the impact of caregivers' genetic risk on well-being may not have been accounted for. With the addition of genetic data to large survey samples, family caregivers' genetic vulnerability to mental and physical health problems can now be estimated. Parents from the Wisconsin Longitudinal Study who have an adult child with an SMI ( = 265) and a comparison group of parents with a child without disabilities ( = 5,036) reported their psychological well-being and mental and physical health across 4 measures. Genetic vulnerability was assessed using polygenic risk scores of neuroticism, bipolar disorder, schizophrenia, and depression. Results indicate that the effect of having a child with an SMI still had significant effects for all 4 parental health outcomes even after controlling for these measures of genetic vulnerability. This study's results affirm the negative health impact of parenting a child with SMI, above and beyond genetic vulnerability. (PsycInfo Database Record (c) 2021 APA, all rights reserved).
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http://dx.doi.org/10.1037/fam0000783DOI Listing
April 2021

Low Zone CGG Repeats: Phenotypic Associations in the Context of Parenting Stress.

Front Pediatr 2020 14;8:223. Epub 2020 May 14.

Waisman Center, University of Wisconsin-Madison, Madison, WI, United States.

The gene on the X chromosome has varying numbers of CGG repeats. The modal number is 30, and expansion to >200 results in fragile X syndrome, but the copy number extends down to 6. Past research suggests that individuals whose CGGs are in the "low zone" (LZ; defined here as ≤ 25 CGGs) may be more environmentally-reactive than those with normal range repeats (26-40 CGGs)-a gene x environment interaction. Using a population-based DNA biobank, in our primary analysis we compared 96 mothers with LZ CGG repeats on both alleles to 280 mothers who had CGG repeats in the normal range. Secondarily, we conducted parallel analyses on fathers. We investigated how parents in these two CGG repeat categories differentially responded to stress, defined as parenting a child with disabilities. Significant gene x environment interactions indicated that LZ mothers who had children with disabilities had greater limitations (in executive functioning, depression, anxiety, daily health symptoms, and balance) than LZ mothers whose children did not have disabilities. In contrast, mothers with normal-range CGG repeats did not differ based on stress exposure. For fathers, a similar pattern was evident for one phenotype only (hand tremors). Although on average LZ CGGs are not associated with compromised functioning, the average masks differential response to the environment.
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http://dx.doi.org/10.3389/fped.2020.00223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7240007PMC
May 2020

Apolipoprotein ɛ4 Allele and Subjective Cognitive Functioning in Parents of Adults With Disabilities.

J Gerontol B Psychol Sci Soc Sci 2020 09;75(8):e189-e197

Waisman Center, University of Wisconsin-Madison.

Objectives: Parents of individuals with disabilities face ongoing responsibilities of providing care and support for their children, even during the child's adulthood. Past research has shown that this caregiving role is linked to chronic stress and subsequent adverse health outcomes for parents, including impaired cognition. This study examines the impacts of genetic risk for cognitive impairment (apolipoprotein [APOE] ɛ4 allele) among parents of adults with disabilities and comparison parents whose adult children do not have disabilities.

Method: We performed rank order regression analysis of data from the Wisconsin Longitudinal Study (2004-2006 and 2010-2012 surveys and DNA samples). Participants included parents of adults with disabilities (247 mothers and 159 fathers) and comparison parents whose adult children were not disabled (1,482 mothers and 954 fathers).

Results: Mothers who had adult children with disabilities and who were APOE ɛ4 carriers reported significantly declining levels of subjective cognitive functioning over time, but mothers of adults with disabilities who did not have the APOE ɛ4 allele did not manifest this change. Among comparison group mothers, cognitive change over time was not a function of their APOE ɛ4 carrier status. Fathers' cognitive function did not differ significantly by either parental status or APOE ɛ4 carrier status.

Discussion: The results show that older mothers of adults with disabilities are more susceptible to cognitive impairment than their age peers if they have the genetic risk factor of APOE ɛ4 allele.
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http://dx.doi.org/10.1093/geronb/gbaa061DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489093PMC
September 2020

Trajectories of Change in the Behavioral and Health Phenotype of Adolescents and Adults with Fragile X Syndrome and Intellectual Disability: Longitudinal Trends Over a Decade.

J Autism Dev Disord 2020 Aug;50(8):2779-2792

University of Wisconsin-Madison Waisman Center, 1500 Highland Avenue, Room 531A, Madison, WI, 53705, USA.

This study examined trajectories of daily living skills, behavior problems, body mass index (BMI), and health conditions spanning nearly a decade in adolescents and adults with fragile X syndrome (N = 134; age range at study end = 19-49 years), examining influences of sex and autism spectrum disorder (ASD) symptoms. Hierarchical linear modeling revealed early increases in daily living skills, with decreases at older ages. Behavior problems became less severe over time, with some increases at older ages. Individuals gained weight and had increasing health problems over time. Fewer ASD symptoms were associated with greater daily living skills and fewer behavior problems at study start. This study offers some of the first prospective quantitative analyses of behavioral and health life course trajectories in FXS.
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http://dx.doi.org/10.1007/s10803-020-04367-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377950PMC
August 2020

Inhibition deficits are modulated by age and CGG repeat length in carriers of the FMR1 premutation allele who are mothers of children with fragile X syndrome.

Brain Cogn 2020 03 27;139:105511. Epub 2019 Dec 27.

Waisman Center, University of Wisconsin-Madison, 1500 Highland Ave, Madison, WI 53705, USA. Electronic address:

Individuals who carry a premutation (PM) allele on the FMR1 gene may experience executive limitations associated with their genetic status, including inhibition deficits. However, poor understanding of individualized risk factors has limited clinical management of this group, particularly in mothers who carry the PM allele who have children with fragile X syndrome (FXS). The present study examined CGG repeat length and age as factors that may account for variable expressivity of inhibition deficits. Participants were 134 carriers of the PM allele who were mothers of children with FXS. Inhibition skills were measured using both self-report and direct behavioral assessments. Increased vulnerability for inhibition deficits was observed at mid-range CGG lengths of approximately 80-100 repeats, with some evidence of a second zone of vulnerability occurring at approximately 130-140 CGG repeats. Risk associated with the genotype also became more pronounced with older age. This study identifies personalized risk factors that may be used to tailor the clinical management of executive deficits in carriers of the PM allele. Inhibition deficits may contribute to poor outcomes in carriers of the PM allele and their families, particularly in midlife and early old age, and clinical monitoring may be warranted.
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http://dx.doi.org/10.1016/j.bandc.2019.105511DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6954879PMC
March 2020

Generativity and Well-Being of Midlife and Aging Parents With Children With Developmental or Mental Health Problems.

Res Aging 2020 Mar-Apr;42(3-4):95-104. Epub 2019 Nov 7.

Waisman Center, University of Wisconsin-Madison, WI, USA.

Parents who have a child with a developmental problem or mental disorder often provide support and assistance to their child throughout their lives, and the burden of caregiving can have an adverse impact on parents' mental and physical health. Using Erikson's theory as a framework, the present study investigated generativity as a moderator of the effects of parenting a child with a disability on parents' well-being during mid- to late life. Using data from the study of Midlife in the United States, we identified 220 parents who had a child with a disability and 3,784 parents whose children did not have a disability. Regression analyses showed that the effect of parenting a child with a disability on negative affect, positive affect, and physical health was conditional on both parental gender and generativity, with mothers experiencing greater adverse effects of parenting but showing a benefit from high levels of generativity.
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http://dx.doi.org/10.1177/0164027519884759DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7031015PMC
November 2019

Effects of parenting adults with disabilities on later-life health: The role of intergenerational ambivalence.

Psychol Aging 2020 Mar 14;35(2):177-189. Epub 2019 Oct 14.

Department of Psychology, University of Hawaii at Manoa.

According to family systems theory, strains from parenting an adult with disabilities may spill over to parents' relationships with their other children and disrupt family dynamics and their well-being in later-life. This study examined whether parental ambivalence toward their nondisabled children is greater in families of adults with disabilities (developmental disabilities [DD] or serious mental illnesses [SMI]) than families without any adult children with disabilities. The study also investigated whether ambivalence mediates the associations between having an adult child with DD or SMI and parents' health. Data were from the 2011 Wisconsin Longitudinal Study in which aging parents (M = 71; n = 6,084) were asked about their relationship with each of their adult children. Multilevel regression models and multilevel structural equation models were estimated to analyze the data. Our findings showed that parents of an adult with SMI felt greater ambivalence toward their nondisabled adult children than comparison group parents of adult children without disabilities, whereas no significant differences were found between parents of an adult child with DD and comparison group parents. Parental ambivalence toward their nondisabled adult children played a significant indirect role in the negative association between having a child with SMI and parental physical and mental health. The findings have implications for clinical practice with aging families of adults with disabilities and suggest the need for additional research to better understand intergenerational parent-adult child dynamics in these families. (PsycINFO Database Record (c) 2020 APA, all rights reserved).
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http://dx.doi.org/10.1037/pag0000413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042070PMC
March 2020

Positive Emotional Support in Premutation Carrier Mothers of Adolescents and Adults With Fragile X Syndrome: Gene by Environment Interactions.

Am J Intellect Dev Disabil 2019 09;124(5):411-426

Sigan L. Hartley, Waisman Center and School of Human Ecology, University of Wisconsin-Madison; Leann S. DaWalt, Jinkuk Hong, Jan S. Greenberg, and Marsha R. Mailick, Waisman Center, University of Wisconsin-Madison.

We examined the benefit of emotional support on daily health in premutation carrier mothers of adolescents and adults with fragile X syndrome ( = 114), and whether this benefit was moderated by the mother's genetic status ( CGG repeat length). In an 8-day daily diary, maternal daily health was assessed subjectively through self-reported number of physical health symptoms and physiologically via cortisol awakening response. Multilevel lagged-day models indicated that premutation carrier mothers with midrange CGG repeats derived less health benefit from a day with high positive emotional support than those with lower or higher numbers of repeats within the premutation range. The data support the influence of both genetic and environmental influences on the health of this population.
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http://dx.doi.org/10.1352/1944-7558-124.5.411DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6948144PMC
September 2019

Mortality in parents after the death of a child.

Soc Sci Med 2019 10 28;239:112522. Epub 2019 Aug 28.

Department of Psychology, University of Hawaii at Manoa, USA. Electronic address:

Objective: The death of a child is a traumatic stressor that takes a toll on the health of parents. This study examined long-term impacts of the death of a child on the risk of early mortality in bereaved parents. In a follow-up analysis, a twin subsample was analyzed to examine potential genetic confounding.

Method: We analyzed data from the Midlife in the United States (MIDUS) study. The primary sample consists of two groups of MIDUS 2 participants (2004-06); (1) parents who experienced the death of a child prior to MIDUS 2 (n = 451) and (2) comparison parents who had not experienced death of any children (n = 1804) (mean age = 63). We also analyzed 52 twin pairs in which one twin experienced the death of a child and 271 twin pairs in which both twins had all living children. Mortality status of parents was assessed in 2017.

Results: Parents who had experienced the death of a child had a 32% higher likelihood of early mortality (defined as dying earlier than life expectancy) than their peers who did not have any deceased children, and they were more likely to die of heart disease. Analyses of the twin subsample revealed significantly lower concordance for early mortality among the pairs with a bereaved twin than among control twins, consistent with non-genetic effects.

Conclusions: The findings suggest that the death of a child has lasting impacts on the risk of early mortality in bereaved parents. This study provides the first U.S. estimate of bereavement effects on mortality extending through the parents' full life course, with significant public health implications. In addition, analysis of concordance of early death rates in the twin subsample suggests the impact on mortality of parental bereavement, net of genetic factors.
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http://dx.doi.org/10.1016/j.socscimed.2019.112522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6802289PMC
October 2019

Data-driven phenotype discovery of premutation carriers in a population-based sample.

Sci Adv 2019 08 21;5(8):eaaw7195. Epub 2019 Aug 21.

Waisman Center, University of Wisconsin-Madison, Madison, WI, USA.

The impact of the premutation on human health is the subject of considerable controversy. A fundamental unanswered question is whether carrying the premutation allele is directly correlated with clinical phenotypes. A challenging problem in past genotype-phenotype studies of the premutation is ascertainment bias, which could lead to invalid research conclusions and negatively affect clinical practice. Here, we created the first population-based -informed biobank to find the pattern of health characteristics in premutation carriers. Our extensive phenotyping shows that premutation carriers experience a clinical profile that is significantly different from controls and is evident throughout adulthood. Comprehensive understanding of the clinical risk associated with this genetic variant is critical for premutation carriers, their families, and clinicians and has important implications for public health.
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http://dx.doi.org/10.1126/sciadv.aaw7195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6703870PMC
August 2019

Conversational Language Is a Predictor of Vocational Independence and Friendships in Adults with ASD.

J Autism Dev Disord 2019 Oct;49(10):4294-4305

Waisman Center, University of Wisconsin-Madison, Madison, WI, 53705, USA.

Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder, impacting social communication and in some individuals, aspects of language such as vocabulary diversity. However, we have only a limited understanding of the verbal language abilities of adults with ASD. The present longitudinal study examined conversational language and its impact on vocational independence and friendship status measured 5 years later in a sample of 84 adults with ASD. After controlling for IQ and childhood language, vocabulary diversity (a measure of structural language) predicted vocational independence and having friendships, while topic maintenance (a measure of social communication) predicted friendships. These findings highlight the importance of adult conversational language abilities for adult outcomes and quality of life.
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http://dx.doi.org/10.1007/s10803-019-04147-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011355PMC
October 2019

Loss in services precedes high school exit for teens with autism spectrum disorder: A longitudinal study.

Autism Res 2019 06 29;12(6):911-921. Epub 2019 Apr 29.

Waisman Center, University of Wisconsin-Madison, Madison, Wisconsin.

The present longitudinal study investigated changes in service receipt and unmet service needs spanning 14 years before and after high school exit in a large community-based sample of individuals with autism spectrum disorder (ASD) (n = 204), of whom 59% had co-occurring intellectual disability (ID). Using multilevel models, potential discontinuity of service patterns at the point of high school exit was examined, as well as the rate of change in services received and needed during the high school years and into the post-high school period. Differences between those with and without ID were probed. Study findings indicated that overall, sample members experienced a reduction in receipt of services during high school, particularly for those without co-occurring ID. After high school exit, sample members experienced a decline in services received; for those without ID, there was a continuous rate of loss of services after leaving high school but for those with ID, there was a sharp decline in services received. Unmet service needs increased right after high school exit for both those with and without ID. These patterns reflect loss of entitlement for services that accompanies high school exit, and the limited availability of adult services for individuals with ASD. This study documented not only the post-high school service cliff that has been the subject of much concern, but also that the loss of services begins long before high school exit and that subgroups of the population with ASD are particularly vulnerable. Autism Res 2019, 12: 911-921. © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In this research, we studied changes in the number of services received before and after high school exit in a large sample of individuals with autism spectrum disorder (ASD). With each passing year during high school, individuals with ASD received fewer services. At the time of high school exit, there was a sharp drop in the number of services received, particularly for those with co-occurring intellectual disability. This study found not only that there is a post-high school service cliff, but also that the loss of services begins long before high school exit.
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http://dx.doi.org/10.1002/aur.2113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546537PMC
June 2019

Genome-wide association study reveals sex-specific genetic architecture of facial attractiveness.

PLoS Genet 2019 04 4;15(4):e1007973. Epub 2019 Apr 4.

Department of Statistics, University of Wisconsin-Madison, Madison, WI, United States of America.

Facial attractiveness is a complex human trait of great interest in both academia and industry. Literature on sociological and phenotypic factors associated with facial attractiveness is rich, but its genetic basis is poorly understood. In this paper, we conducted a genome-wide association study to discover genetic variants associated with facial attractiveness using 4,383 samples in the Wisconsin Longitudinal Study. We identified two genome-wide significant loci, highlighted a handful of candidate genes, and demonstrated enrichment for heritability in human tissues involved in reproduction and hormone synthesis. Additionally, facial attractiveness showed strong and negative genetic correlations with BMI in females and with blood lipids in males. Our analysis also suggested sex-specific selection pressure on variants associated with lower male attractiveness. These results revealed sex-specific genetic architecture of facial attractiveness and provided fundamental new insights into its genetic basis.
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http://dx.doi.org/10.1371/journal.pgen.1007973DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6448826PMC
April 2019

Validating psychosocial pathways of risk between neuroticism and late life depression using a polygenic score approach.

J Abnorm Psychol 2019 Apr 4;128(3):200-211. Epub 2019 Mar 4.

Waisman Center, University of Wisconsin-Madison.

Neuroticism is a stable and heritable personality trait that is strongly linked to depression. Yet, little is known about its association with late life depression, as well as how neuroticism eventuates into depression. This study used data from the Wisconsin Longitudinal Study (WLS; N = 4,877) to examine the direct and indirect effects of neuroticism on late life depression at 3 points in the life course-ages 53, 64, and 71-via stressful life events (i.e., independent and dependent) and social supports measured across adulthood and into later life. Neuroticism was assayed using multiple methods, including self-report measures (phenotypic model) and a polygenic score (polygenic model) informed by a meta-analytic genome-wide association study. Results indicated that the phenotypic model of neuroticism and late life depression was partially mediated via dependent stressful life events experienced after the age of 53 and by age 64 social support. This association was replicated in the polygenic model of neuroticism, providing key evidence that the findings are robust. No indirect effects emerged with respect to age 53 social support, age 71 social support, adult dependent stressful life events (experienced between age 19 and 52), and adult and late life independent stressful life events in either the phenotypic or polygenic models as they pertained to late life depression. Results are consistent with previous findings that individuals with high neuroticism may be vulnerable to late life depression through psychosocial risk factors that are, in part, attributable to their own personality. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/abn0000419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6462143PMC
April 2019

Mortality in individuals with autism spectrum disorder: Predictors over a 20-year period.

Autism 2019 10 28;23(7):1732-1739. Epub 2019 Feb 28.

University of Wisconsin-Madison, USA.

Research has shown that individuals with autism spectrum disorder have higher rates of health problems throughout childhood, adolescence, and adulthood, and that this may result in elevated risk of early mortality. This study reported the rate, timing, and causes of death in a large community-based cohort of adolescents and adults with autism spectrum disorder ( = 406) over a 20-year period (1998-2018) and identified predictors of mortality. Over this period, 6.4% of individuals died at an average age of 39 years. Causes of death included chronic conditions (such as cancer and heart disease), accidents (such as choking on food and accidental poisoning), and health complications due to medication side effects. Even after controlling for age and health status, significant predictors of mortality were early childhood levels of impairments in social reciprocity and high levels of functional impairments at the start of the study period. The results suggest the importance of social engagement and functional self-sufficiency across the life course, as well as adequate access to health care for individuals with autism spectrum disorder.
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http://dx.doi.org/10.1177/1362361319827412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6713622PMC
October 2019

Health of parents of individuals with developmental disorders or mental health problems: Impacts of stigma.

Soc Sci Med 2018 11 15;217:152-158. Epub 2018 Oct 15.

School of Social Work and Waisman Center, University of Wisconsin-Madison, Madison, USA. Electronic address:

Objective: Parents of individuals with developmental disorders or mental health problems often provide life-long care and support to their children, which negatively affects their health in part due to chronic stress. This study aimed to examine the experience of stigma as a source of chronic stress among parents of individuals with developmental disorders or mental health problems and the effect of stigma on parental health outcomes.

Method: Using data from the Survey of Midlife in the United States (MIDUS 2 and 3), we constructed a sample for a longitudinal analysis including 128 parents of individuals with developmental disorders (e.g., autism, cerebral palsy, epilepsy, Down syndrome, intellectual disabilities, brain injury, ADD/ADHD) or mental health problems (e.g., bipolar disorder, schizophrenia, major depression) and 2256 parents whose children were nondisabled.

Results: Parents who had children with developmental disorders or mental health problems prior to the beginning of the study (i.e., at MIDUS 1) reported higher levels of stigma related to embarrassment/shame and daily discrimination than parents of nondisabled individuals ten years later at MIDUS 2, which in turn were associated with poorer parental health outcomes (poorer self-rated health and a greater number of chronic conditions) nearly a decade after that at MIDUS 3.

Conclusions: The findings suggest that the stigma associated with parenting a child with disabilities may be one mechanism that places such parents at risk for poor health. Efforts to alleviate the stigma associated with developmental disorders or mental health problems may have beneficial effects on health of parents of individuals with such conditions.
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http://dx.doi.org/10.1016/j.socscimed.2018.09.044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6202233PMC
November 2018

Unaffected siblings of adolescents and adults with fragile X syndrome: Effects on maternal well-being.

J Fam Psychol 2019 Jun 13;33(4):487-492. Epub 2018 Sep 13.

Waisman Center.

The present study investigated the effects of children without disabilities on maternal physical and mental health in families with adolescents or adults with fragile X syndrome. Mothers with the premutation ( = 87) reported on behavior problems and functional limitations of their adolescent or adult child with fragile X syndrome and their own physical and mental health. Mothers also provided a blood sample to determine CGG repeat length. The proportion of unaffected children in the family significantly buffered the effect of both child behavior problems and functional limitations on maternal self-rated health, such that having a higher proportion of unaffected children in the family had a protective effect on maternal health when the target child had more severe behavior problems and functional limitations. There was a similar buffering process for maternal depressive symptoms but at a trend level. Additionally, maternal CGG repeat length had a significant curvilinear association with self-rated health, indicating that mothers with midrange repeat lengths reported the poorest health, whereas mothers with lower and higher repeat lengths in the premutation range reported better health. The data suggest that unaffected children in the family may be an important resource for premutation carrier mothers. Findings are consistent with previous research indicating that mothers with varying levels of genetic liability have variable risk for health problems. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
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http://dx.doi.org/10.1037/fam0000458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6416081PMC
June 2019

Curvilinear Association Between Language Disfluency and CGG Repeat Size Across the Normal, Intermediate, and Premutation Range.

Front Genet 2018 24;9:344. Epub 2018 Aug 24.

Department of Psychology, University of South Carolina, Columbia, SC, United States.

Historically, investigations of have focused almost exclusively on the clinical effects of CGG expansion within the categories of the premutation (55-200 CGG repeats) and fragile X syndrome (>200 CGG repeats). However, emerging evidence suggests that CGG-dependent phenotypes may occur across allele sizes traditionally considered within the "normal" range. This study adopted an individual-differences approach to determine the association between language production ability and CGG repeat length across the full range of normal, intermediate, and premutation alleles. Participants included 61 adult women with CGG repeats within the premutation ( = 37), intermediate (i.e., 41-54 repeats; = 2), or normal (i.e., 6-40 repeats; = 22) ranges. All participants were the biological mothers of a child with a developmental disorder, to control for the potential effects of parenting stress. Language samples were collected and the frequency of language disfluencies (i.e., interruptions in the flow of speech) served as an index of language production skills. Verbal inhibition skills, measured with the Hayling Sentence Completion Test, were also measured and examined as a correlate of language disfluency, consistent with theoretical work linking language disfluency with inhibitory deficits (i.e., the Inhibition Deficit Hypothesis). Blood samples were collected to determine CGG repeat size. A general linear model tested CGG repeat size of the larger allele (allele-2) as the primary predictor of language disfluency, covarying for education level, IQ, age, and CGG repeats on the other allele. A robust curvilinear association between CGG length and language disfluency was detected, where low-normal (∼ <25 repeats) and mid-premutation alleles (∼90-110 repeats) were linked with higher rates of disfluency. Disfluency was not associated with inhibition deficits, which challenges prior theoretical work and suggests that a primary language deficit could account for elevated language disfluency in associated conditions. Findings suggest CGG-dependent variation in language production ability, which was evident across individuals with and without CGG expansions on
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http://dx.doi.org/10.3389/fgene.2018.00344DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6118037PMC
August 2018

Health Profiles of Mosaic Versus Non-mosaic Premutation Carrier Mothers of Children With Fragile X Syndrome.

Front Genet 2018 16;9:173. Epub 2018 May 16.

Department of Pediatrics, Rush University Medical Center, Chicago, IL, United States.

The premutation is of increasing interest to the FXS community, as questions about a primary premutation phenotype warrant research attention. 100 premutation carrier mothers (mean age = 58; 67-138 CGG repeats) of adults with fragile X syndrome were studied with respect to their physical and mental health, motor, and neurocognitive characteristics. We explored the correlates of CGG repeat mosaicism in women with expanded alleles. Mothers provided buccal swabs from which DNA was extracted and the CGG genotyping was performed (Amplidex Kit, Asuragen). Mothers were categorized into three groups: Group 1: premutation non-mosaic ( = 45); Group 2: premutation mosaic ( = 41), and Group 3: premutation/full mutation mosaic ( = 14). Group 2 mothers had at least two populations of cells with different allele sizes in the premutation range besides their major expanded allele. Group 3 mothers had a very small population of cells in the full mutation range (>200 CGGs) in addition to one or multiple populations of cells with different allele sizes in the premutation range. Machine learning (random forest) was used to identify symptoms and conditions that correctly classified mothers with respect to mosaicism; follow-up comparisons were made to characterize the three groups. In categorizing mosaicism, the random forest yielded significantly better classification than random classification, with overall area under the receiver operating characteristic curve (AUROC) of 0.737. Among the most important symptoms and conditions that contributed to the classification were anxiety, menopause symptoms, executive functioning limitations, and difficulty walking several blocks, with the women who had full mutation mosaicism (Group 3) unexpectedly having better health. Although only 14 premutation carrier mothers in the present sample also had a small population of full mutation cells, their profile of comparatively better health, mental health, and executive functioning was unexpected. This preliminary finding should prompt additional research on larger numbers of participants with more extensive phenotyping to confirm the clinical correlates of low-level full mutation mosaicism in premutation carriers and to probe possible mechanisms.
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http://dx.doi.org/10.3389/fgene.2018.00173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5964198PMC
May 2018

Using machine learning to identify patterns of lifetime health problems in decedents with autism spectrum disorder.

Autism Res 2018 08 7;11(8):1120-1128. Epub 2018 May 7.

Waisman Center, University of Wisconsin-Madison, 1500 Highland Ave, Madison, WI, 53705.

Very little is known about the health problems experienced by individuals with autism spectrum disorder (ASD) throughout their life course. We retrospectively analyzed diagnostic codes associated with de-identified electronic health records using a machine learning algorithm to characterize diagnostic patterns in decedents with ASD and matched decedent community controls. Participants were 91 decedents with ASD and 6,186 sex and birth year matched decedent community controls who had died since 1979, the majority of whom were middle aged or older adults at the time of their death. We analyzed all ICD-9 codes, V-codes, and E-codes available in the electronic health record and Elixhauser comorbidity categories associated with those codes. Diagnostic patterns distinguished decedents with ASD from decedent community controls with 75% sensitivity and 94% specificity solely based on their lifetime ICD-9 codes, V-codes, and E-codes. Decedents with ASD had higher rates of most conditions, including cardiovascular disease, motor problems, ear problems, urinary problems, digestive problems, side effects from long-term medication use, and nonspecific lab tests and encounters. In contrast, decedents with ASD had lower rates of cancer. Findings suggest distinctive lifetime diagnostic patterns among decedents with ASD and highlight the need for more research on health outcomes across the lifespan as the population of individuals with ASD ages. As a large wave of individuals with ASD diagnosed in the 1990s enters adulthood and middle age, knowledge about lifetime health problems will become increasingly important for care and prevention efforts. Autism Res 2018, 11: 1120-1128. © 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study looked at patterns of lifetime health problems to find differences between people with autism who had died and community controls who had died. People with autism had higher rates of most health problems, including cardiovascular, urinary, respiratory, digestive, and motor problems, in their electronic health records. They also had lower rates of cancer. More research is needed to understand these potential health risks as a large number of individuals with autism enter adulthood and middle age.
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http://dx.doi.org/10.1002/aur.1960DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6203659PMC
August 2018

Lifelong Parenting of Adults With Developmental Disabilities: Growth Trends Over 20 Years in Midlife and Later Life.

Am J Intellect Dev Disabil 2018 05;123(3):228-240

Frank J. Floyd, Psychology Department, University of Hawaii at Manoa.

This research examined how parenting adults with developmental disabilities affects parental well-being beyond midlife and into old age. Parents of adults with developmental disabilities ( n = 249) and parents of adults without disabilities ( n = 9,016), studied in their early 50s and mid-60s, were longitudinally tracked into their early 70s. Compared to parents of adults without disabilities, parents of adults with disabilities showed a pattern of normative functioning in their 50s, followed by poorer well-being in their mid-60s, and further declines in health and well-being into the early 70s. Aging parents who co-resided with their adult child with disabilities were particularly vulnerable, experiencing a steeper increase in depressive symptoms and body mass index (BMI) than parents whose child with disabilities lived away from home.
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http://dx.doi.org/10.1352/1944-7558-123.3.228DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6442468PMC
May 2018

Friendships and social participation as markers of quality of life of adolescents and adults with fragile X syndrome and autism.

Autism 2019 02 12;23(2):383-393. Epub 2017 Dec 12.

University of Wisconsin-Madison, USA.

Friendships and social participation are key domains of quality of life for individuals with intellectual disabilities. This study examined the friendships, social and recreational activities, and family social networks of individuals with intellectual disabilities from two distinct diagnostic groups: individuals diagnosed with fragile X syndrome (n = 81) compared with those diagnosed with autistic disorder (n = 226). Within each diagnostic group, individuals in two developmental stages were compared: adolescence and adulthood. Quality of life in friendships and social participation domains was notably low for individuals with fragile X and those with autism. Individuals with fragile X had more friendships and a less negative social impact on the family than individuals with autism. Across both groups, adolescents spent less time with friends and neighbors, and more time in exercising, than did adults.
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http://dx.doi.org/10.1177/1362361317709202DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062207PMC
February 2019
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